chr11-3811260-A-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_014489.4(PGAP2):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000685 in 1,460,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PGAP2
NM_014489.4 start_lost
NM_014489.4 start_lost
Scores
4
9
3
Clinical Significance
Conservation
PhyloP100: 6.46
Genes affected
PGAP2 (HGNC:17893): (post-GPI attachment to proteins 2) The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_014489.4 (PGAP2) was described as [Pathogenic] in ClinVar as 694699
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-3811260-A-G is Pathogenic according to our data. Variant chr11-3811260-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1678531.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGAP2 | NM_014489.4 | c.1A>G | p.Met1? | start_lost | 2/7 | ENST00000278243.9 | |
LOC124902618 | XR_007062559.1 | n.457T>C | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGAP2 | ENST00000278243.9 | c.1A>G | p.Met1? | start_lost | 2/7 | 1 | NM_014489.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249458Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134790
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460332Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726470
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Cologne University | Apr 01, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;D;D;.;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;.;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;.;.;.;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D
Polyphen
D;.;.;.;.;.;.;P;.
Vest4
MutPred
Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;.;.;.;.;.;.;
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at